Nitro thioethers

Low temperature irradiation of the glycoside thiohydroxamates (178) in the presence of 2-nitropropene gives clean formation of adducts (179). Conversion of the geminal nitro thioether function to a ketone and removal of the chiral auxiliary yields the free aldol product (180) in >90% enantiomeric excess. Single stranded aminoethylglycine dimers (181) and (182) differ only in whether... 

Nitro-l-pheriylethyl Thioether RSCH(C6H5)CH2N02 (Chart 7)... 

K2CO3 or CS2CO3, DMF or CH3CN, PhSH, 88-96% yield. This process is not always selective for p-nosylate cleavage. Some amines, especially cyclic ones, tend to form 4-phenyl thioethers by nitro displacement as by-products of the cleavage process. This seems to be true only for the p-nosylate. ... 

Thioethers 210 are smoothly formed upon cyclization of silyl nitronates 209, generated in situ from the nitro compounds 208, on treatment with N,0-bis(trimethylsilyl)acetamide (BSA, Scheme 24) [57]. Fluorodesilylation of 210 gave the AT-oxide 212, presumably via highly reactive aldehyde 211, which was reduced to the target compound actinidine 213 in an overall 27% yield. 

No sulfoxide complexes of osmium have been reported. Unsymmetri-cal dialkyl sulfoxides have been utilized in extraction studies, and methyl-4,8-dimethylnonyl sulfoxide has found application in the extraction of iron (266). Extraction of ruthenium from hydrochloric acid solutions by sulfoxides has been studied (470) and comparisons of sul-fones, sulfoxides, and thioethers as extractants for nitrosoruthenium species reported (441, 443). Similar studies on the extraction of nitro-soosmium species have been reported (442). 

Finally, replacement of the methylene bridge by a sulfur bridge leads to compoxmds such as 117 and 123 which are major tranquilizers. Thus, Ullmann condensation of thiosalicylic acid 112 with ortho-chloronitrobenzene affords thioether 113 the nitro group is then reduced to the aniline (114). Cycliza-tion as above leads to the lactam 115, which is then converted to the iminochloride derivative (116). Condensation with N-methylpiperazine affords clothiapine... 

Nucleophilic aromatic displacement is invoked for incorporation of the side chain in yet another benzimidazole. Thus, treatment of 2,5-dinitroacetanrlide (52-1) with the anion from mercaptomethylcyclohexane leads to the unusual displacement of one of the nitro groups and the formation of thioether (52-3). This intermediate is then converted to diamine (52-4) by sequential reduction and hydrolysis of the amide. Condensation with the same thiourea derivative as above affords dribenda-zole (52-5) [55]. 

An alternate and more controlled approach to the synthesis of phenothiazines involves sequential aromatic nucleophilic displacement reactions. This alternate scheme avoids the formation of the isomeric products that are sometimes observed to form from the sulfuration reaction when using substituted aryl rings. The first step in this sequence consists of the displacement of the activated chlorine in nitrobenzene (30-1) by the salt from orf/io-bromothiophenol (30-2) to give the thioether (30-3). The nitro group is then reduced to form aniline (30-4). Heating that compound in a solvent such as DMF leads to the internal displacement of bromine by amino nitrogen and the formation of the chlorophenothiazine (30-4). Alkylation of the anion from that intermediate with 3-chloro-l-dimethylaminopropane affords chlorpromazine (30-5) [31]. 

Yet another approach to these compounds consists of substituting the piperazine ring onto the preformed heterocyclic moiety. Ullman condensation of the substituted thiosalyciclic acid (40-1) with ort/zo-chloronitrobenzene results in the displacement of chlorine by thiophenoxide and the formation of the thioether (40-2). The nitro group in this last intermediate is then reduced to an aniline (40-3) the resulting amino acid is then cyclized thermally to the lactam (40-4). Treatment of that with phosphorus oxychloride gives the imino chloride (40-5). Reaction with N-methylpiperazine leads to the replacement of chlorine by nitrogen and the formation of clothiapine (40-6) [39]. 

Figure 27.18 Common configuration for postcolumn reactors with electrochemical analysis. (A) LC-chemical reaction-EC. Postcolumn addition of a chemical reagent (for example, Cu2+ or an enzyme). (B) LC-enzyme-LC. Electrochemical detection following postcolumn reaction with an immobilized enzyme or other catalyst (for example, dehydrogenase or choline esterase). (C) LC-EC-EC. Electrochemical generation of a derivatizing reagent. The response at the second electrode is proportional to analyte concentration (for example, production of Br2 for detection of thioethers). (D) LC-EC-EC. Electrochemical derivatization of an analyte. In this case a compound of a more favorable redox potential is produced and detected at the second electrode (for example, detection of reduced disulfides by the catalytic oxidation of Hg). (E) LC-hv-EC. Photochemical reaction of an analyte to produce a species that is electrochemically active (for example, detection of nitro compounds and phenylalanine). Various combinations of these five arrangements have also been used. [Reprinted with permission from Bioanalytical Systems, Inc.]...

Thiol B.P. °C (/mmHg) M.P. °C 2,4- Dinitro- phenyl- thioether °C 2,4- Dinitro- phenyl- sulphone °C 3,5- Dinitro- thio- benzoate °C Hydrogen 3-nitro- thio- phthalate... 

If SnAr reactions are to be performed, it is advisable to render the scaffold as electron deficient as possible. Thus, thioethers may be oxidized to sulfoxide or sulfonyl groups, and nitrogen-containing functionahties should be amides or nitro groups prior to a substitution. Of course, these derivati-zations are limited by the reactivity of the corresponding heterocycle, since more than one functionality may be displaced, if multiple leaving groups are present. 

To facilitate the nitro group displacement reaction, the thioethers 7, obtained by treatment of difluoride 6 with thiols, were oxidized with 3-chloroperbenzoic acid to afford the corresponding sulfones 8 (Fig. 4). The resulting sulfones 8 showed the expected high reactivity toward nucleophiles, as demonstrated by the efficient displacement of both the second fluoride and the nitro group with two different aliphatic amines to yield the highly substituted benzamides 10. 

G. Boche, The Structure of Lithium Compounds of Sulfones, Sulfoximides, Sulfoxides, Thioethers and 1,3-Dithianes, Nitriles, Nitro Compounds and Hydrazones, Angew. Chem. Int. Ed. Engl. 1989, 28, 277-297. 

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